CHEMISTRY OF NUCLEOSIDES AND NUCLEOTIDES 



171 



They show the properties of diesters of phosphoric acid (ion-exchange and 

 electrophoresis) and are converted by acids or further action of ribonuclease 

 into mixtures of the a and b isomers.^''^' '^^ These properties are consitent 

 with those expected for nucIeoside-2',3'-hydrogen phosphates, and this has 

 been estabhshed by direct comparison of the natural substances with syn- 

 thetic cytidine-2',3'-hydrogen phosphate (XXXIV) and uridine-2',3'- 

 hydrogen phosphate."^ 



■0- 



OH 



\/ 

 P 



1 I 



-CH-CH-CH-CH-CHrOH 



-0- 



OH 



^/ 

 P 



I I 



L-CH-CH-CH-CH-CH,-OH 



N. 



N 

 NH2 



XXXIV 



Cytidine-2',3'-hydrogen phosphate 



N. ^N 



NH2 



N 



XXXV 



Adenosme-2',3'-hjdrogen phosphate 



CycUc phosphates of adenosine (XXXV) and guanosine are produced, in 

 addition to the cyclic pyrimidine nucleotides, by very mild alkaline hy- 

 drolysis of ribonucleic acid.^^^ The cyclic purine nucleotides, although read- 

 ily hydrolyzed by acids to the a and b isomers, are not attacked by ribo- 

 nuclease.'^^ The structure of the adenine nucleotide is fully established by 

 comparison with synthetic adenosine-2',3'-hydrogen phosphate. 



k. Deoxyribosc Nucleotides 



As mentioned before, enzymic or chemical hydrolysis of deoxyribonucleic 

 acid gives pyrimidine deoxyribonucleotides, whereas purine deoxyribonu- 

 cleotides can only be prepared enzymically. Four monophosphates of the 

 deoxynucleosides have been isolated, namely: thymidylic acid, cytosine 

 deoxyriboside phosphate, adenine deoxyriboside phosphate (XXXVI), and 

 guanine deoxyriboside phosphate. "''■'^^ In addition a fifth, 5-methylcytosine 

 deoxyriboside phosphate, has been demonstrated in deoxyribonucleic acid 

 hydrolysates by ion-exchange methods.''^ Until recently the phosphate 

 group in the deoxynucleotides was thought to be situated at position 3' in 

 the sugar chain. In the deoxynucleotides isomerism of the type shown by 

 the ribonucleoside-2'- and -3'-phosphates is not possible and by analogy 

 with these ribonucleotides the 3'-position was thought to be phosphorylated. 

 The isolation of 5'-phosphates from ribonuclease digests of ribonucleic acid 

 invalidates these earlier assumptions. Furthermore, the deoxyribonucleo- 



>9^ W. E. Cohn, J. Am. Chem. Soc. 73, 1539 (1951). 



